When tuning up various parts of a liquid chromatograph mass spectrometer (LC/MS), the mass spectrometer uses a sample containing components of known types and densities. The tuning as referred to herein involves optimizing control parameters related to analysis conditions such as applied voltages of various parts, temperatures of an ionization probe, and a gas flow rate for the purpose of mass-to-charge ratio (m/z) calibration, mass resolution adjustment, and sensitivity adjustment. The tuning involves monitoring a signal strength corresponding to an amount of ions originating from a target component in the sample and searching for parameter values which maximize the signal strength while changing values of the control parameters to be adjusted. Therefore, a certain amount of time is required to find optimal values of the control parameters, and conventionally it is general practice to use an infusion method to introduce the sample into an ion source. The infusion method is a technique which continuously introduces a liquid sample into the ion source using a syringe pump or the like, and the method enables stable analysis for a relatively extended period of time, but has the disadvantage of involving high sample consumption.
In contrast, a flow injection (FIA) method is a technique which injects a predetermined quantity of a sample into a mobile phase flowing at a constant rate, using an injector for liquid chromatograph or the like, and introduces the sample into an ion source together with the mobile phase (see Patent Document 1 and other documents). Consequently, the flow injection method uses a far smaller quantity of the sample than the infusion method described above. However, in the case of the FIA method, the time when the sample is introduced into the ion source is considerably limited, and moreover the density of the target component broadens to a bell-shaped (or peak-shaped) distribution with the passage of time. Therefore, when a sample is introduced by the FIA method, the data collecting time in an equipment tuning is greatly restricted compared to the infusion method.
As an example of equipment tuning, description will be given below of a case in which collision energy used for collision-induced dissociation (CID) of ions is optimized on a triple quadrupole mass spectrometer capable of MS/MS analysis. Since the collision energy possessed by the ions at the time of a dissociation operation depends on the voltages applied to the collision cell, ion optical elements in the preceding stage, and the like, the collision energy discussed here is actually the voltages which determine the collision energy.
Generally, the manner of CID-based ionic dissociation varies with the collision energy. Therefore, for the same precursor ions, an optimal value of the collision energy may vary with intended product ions. Thus, in the case of MS/MS analysis, such as multiplex reaction monitoring (MRM) measurement, in which the mass-to-charge ratio of the product ions is fixed, if there are multiple types of intended product ions, the optimal value of collision energy needs to be found for each type of the product ions.
Patent Document 2 describes a known technique for detecting respective intensities of plural product ions generated when predetermined precursor ions are dissociated at plural levels of collision energy set beforehand. With this analysis method, all combinations of the levels of collision energy and plural product ions are analyzed in one cycle, and the intensities of each product ion at different levels of collision energy are obtained by repeating this cycle.
However, with a technique which comprehensively acquires ion intensities as described above, if an appropriate range of collision energy is totally unknown, it is necessary to measure the intensity of each product ion by changing the value at relatively small intervals over a considerably wide range of collision energy. This increases the number of data items to be acquired during one cycle, or increases the duration of each cycle if data acquisition time intervals are kept constant. With the FIA method, since the density of a sample component introduced into the ion source changes to a bell-shaped (peak-shaped) distribution as described above, it is difficult to find the optimal value of collision energy based solely on analysis results of a single cycle. This makes it necessary to find the optimal value of collision energy by accumulating the ion intensity values for several cycles. If, however, the time required for one cycle is long as described above, it might not be possible to find the optimal value within the time period when the target component is being introduced into the ion source. When the optimal value of collision energy is not found within a single sample injection by FIA, another analysis needs to be conducted by injecting the same sample again, which brings about problems of increased sample consumption as well as elongated time required for tuning.
The above problems arise not only in the optimization of collision energy, but also in the optimization of other control parameters of the mass spectrometer, including a lens voltage applied to an ion lens, gas flow rates of nebulizer gas and drying gas used for an ion source in an electrospray ionization (ESI) method or atmospheric pressure chemical ionization (APCI) method, heating temperatures of the ion source and a heating capillary for transporting the generated ions from the ion source to a subsequent stage, and laser intensity in an atmospheric pressure photoionization (APPI) ion source.